NM_005219.5(DIAPH1):c.3809G>T (p.Arg1270Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 24, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001319422.8

Allele description [Variation Report for NM_005219.5(DIAPH1):c.3809G>T (p.Arg1270Leu)]

NM_005219.5(DIAPH1):c.3809G>T (p.Arg1270Leu)

Gene:

DIAPH1:diaphanous related formin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_005219.5(DIAPH1):c.3809G>T (p.Arg1270Leu)

HGVS:

NC_000005.10:g.141516861C>A
NG_011594.2:g.107195G>T
NM_001079812.3:c.3782G>T
NM_001314007.2:c.*109G>T
NM_005219.5:c.3809G>TMANE SELECT
NP_001073280.1:p.Arg1261Leu
NP_005210.3:p.Arg1270Leu
LRG_1117t1:c.3782G>T
LRG_1117t2:c.3809G>T
LRG_1117:g.107195G>T
LRG_1117p1:p.Arg1261Leu
LRG_1117p2:p.Arg1270Leu
NC_000005.9:g.140896428C>A
NG_011594.1:g.107195G>T

Protein change:

R1261L

Links:

dbSNP: rs371664456

NCBI 1000 Genomes Browser:

rs371664456

Molecular consequence:

NM_001314007.2:c.*109G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001079812.3:c.3782G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005219.5:c.3809G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal dominant nonsyndromic hearing loss 1
Synonyms:: KONIGSMARK SYNDROME; Deafness, autosomal dominant 1; DEAFNESS, AUTOSOMAL DOMINANT 1, WITH OR WITHOUT THROMBOCYTOPENIA
Identifiers:: MONDO: MONDO:0007424; MedGen: C1852282; Orphanet: 90635; OMIM: 124900

Name:: Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
Synonyms:: Seizures, cortical blindness, and microcephaly syndrome
Identifiers:: MONDO: MONDO:0014714; MedGen: C5567650; OMIM: 616632

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001510164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001510164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 24, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001510164.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with DIAPH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 1270 of the DIAPH1 protein (p.Arg1270Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2025

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